This is a proposal to carry forward studies of diverse aspects of thyroid hormone economy as they relate to the normal ohysiology of the thyroid andits hormones in man and animals andto the pathogenesis and psthophysiology of thyroid diseases. Studies are planned in four major area of investigation: 1) the peripheral metabolism of thyroid hormones; 2) the mechanism of action of thyroid hormones; 3) regulation of thyroid cell grwoth; and 4) the pathogenesis and pathophysiology of Graves' disease and other autoimmune diseases. Studies of thyroid hormone metabolism will concentrate on a newly-documented pathway of hormone metabolism, cleavage of the other link of the iodothyronine molecule, and will be directed toward quantitating its activity in man and in rats and determing the factors that influence its activity. Studies of the mechanism of action of thyroid hormones will concentrate on those mediated at the plasma membrane and will attempt to determine whether effects of this nature observed in thymic lymphocytes reflect a general and similar response in bodily tissues. Studies of the factors that influence thyroid cell growth will, in part, extend observations concerning the effects of tissue growth factors on the growth and function of thyroid cells in culture and will seek to elucidate their mechanism of action. In addition, the contribution of antibodies that stimulate or inhibit thyroid growth to the pathogenesis of various thyroid diseases will be evaluated and their interaction with tissue growth factors will be explored. Studies of the pathogenesis of Graves' disease have several objectives: to establish an animal model of Graves' disease by immunizing them with unique antigens, including bacter-extracts, that contain TSH receptors; to explore the relationship of other bacterial antigens to the pathogenesis of other thyroid diseases, to elucidate the effects of various lymphokines on the thyroid follicular cell and to explore their interaction with growth factors and antibodies.